Human gamma/delta T-cell proliferation and IFN-gamma production induced by hexamethylene diisocyanate.

Abstract

The human immune response to isocyanate, a leading cause of occupational asthma, remains incompletely characterized, including the cell types involved and the form of the chemical that acts as an antigen. The purpose of this investigation was to characterize human T cells that respond to hexamethylene diisocyanate (HDI), an aliphatic isocyanate routinely used in the automobile body industry. Human T-cell lines were generated and characterized from peripheral blood of HDI-exposed and HDI-unexposed subjects, using two different HDI antigens, HDI-conjugated albumin and HDI-exposed human airway epithelial cells (NCI-H292). Flow cytometry was used to characterize the phenotype of HDI-responsive T cells. ELISA and intracellular staining techniques were used to evaluate HDI-induced cytokine production. DNA sequence analysis of T-cell receptors was used to further define clonal populations of HDI-responsive T cells. HDI antigen preparations but not "mock exposed" control antigens lead to increased proliferation of specific cell types, CD3+CD4-CD8(dim) and/or CD3+CD4-CD8- cells, from HDI-exposed but not from HDI-unexposed subjects. These HDI-responsive T cells expressed unique oligoclonal gamma/delta rather than alpha/beta T-cell receptors, with characteristics suggestive of antigen-mediated selection and specificity. The HDI-stimulated gamma/delta T cells were associated with T(H)1-like cytokines and produce IFN-gamma but not IL-5 or IL-13. These data are the first to demonstrate that HDI can selectively stimulate gamma/delta T cells with the potential to modulate the human immune response to exposure.